Bubonic and septicemic plague is generally spread by flea bites or handling an infected animal.[1] The pneumonitic form is generally spread between people through the air via infectious droplets.[1] Diagnosis is typically by finding the bacterium in fluid from a lymph node, blood or sputum.[2]

Globally about 600 cases are reported a year.[2] In 2017 the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru.[2] In the United States infections occationally occur in rural areas and the bacteria is believed to circulate among rodents.[5] It has historically occurred in large outbreaks, with the most well known being the Black Death in the 14th century, which resulted in greater than 50 million dead.[2]

Swollen inguinal lymph glands on a person infected with the bubonic plague. The swollen lymph glands are termed buboes from the Greek word for groin, swollen gland: bubo.

When a flea bites a human and contaminates the wound with regurgitated blood, the plague carrying bacteria are passed into the tissue. Y. pestis can reproduce inside cells, so even if phagocytosed, they can still survive. Once in the body, the bacteria can enter the lymphatic system, which drains interstitial fluid. Plague bacteria secrete several toxins, one of which is known to cause beta-adrenergic blockade.[6]

Lymphatics ultimately drain into the bloodstream, so the plague bacteria may enter the blood and travel to almost any part of the body. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation (DIC), causing tiny clots throughout the body and possibly ischemic necrosis (tissue death due to lack of circulation/perfusion to that tissue) from the clots. DIC results in depletion of the body's clotting resources, so that it can no longer control bleeding. Consequently, there is bleeding into the skin and other organs, which can cause red and/or black patchy rash and hemoptysis/hematemesis (coughing up/ vomiting of blood). There are bumps on the skin that look somewhat like insect bites; these are usually red, and sometimes white in the center. Untreated, septicemic plague is usually fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent.[11][12][13] People who die from this form of plague often die on the same day symptoms first appear.[citation needed]

The pneumonic form of plague arises from infection of the lungs. It causes coughing and sneezing and thereby produces airborne droplets that contain bacterial cells and are likely to infect anyone inhaling them. The incubation period for pneumonic plague is short, usually two to four days, but sometimes just a few hours. The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness and spitting or vomiting of blood. The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases mortality is nearly 100%.[14][15]

The Oriental rat flea (Xenopsylla cheopsis) engorged with blood after a blood meal. This species of flea is the primary vector for the transmission of Yersinia pestis, the organism responsible for bubonic plague in most plague epidemics in Asia, Africa and South America. Both male and female fleas feed on blood and can transmit the infection.

indirect contact – usually by touching soil contamination or a contaminated surface

airborne transmission – if the microorganism can remain in the air for long periods

fecal-oral transmission – usually from contaminated food or water sources

vector borne transmission – carried by insects or other animals.

Yersinia pestis circulates in animal reservoirs, particularly in rodents, in the natural foci of infection found on all continents except Australia. The natural foci of plague are situated in a broad belt in the tropical and sub-tropical latitudes and the warmer parts of the temperate latitudes around the globe, between the parallels 55 degrees North and 40 degrees South.[16]
Contrary to popular belief, rats did not directly start the spread of the bubonic plague. It is mainly a disease in the fleas (Xenopsylla cheopis) that infested the rats, making the rats themselves the first victims of the plague. Infection in a human occurs when a person is bitten by a flea that has been infected by biting a rodent that itself has been infected by the bite of a flea carrying the disease. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to starve. The flea then bites a host and continues to feed, even though it cannot quell its hunger, and consequently the flea vomits blood tainted with the bacteria back into the bite wound. The bubonic plague bacterium then infects a new person and the flea eventually dies from starvation. Serious outbreaks of plague are usually started by other disease outbreaks in rodents, or a rise in the rodent population.[17]

Since human plague is rare in most parts of the world, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported cases, particularly if their travel is limited to urban areas with modern hotels. The CDC thus only recommends vaccination for: (1) all laboratory and field personnel who are working with Y. pestis organisms resistant to antimicrobials: (2) people engaged in aerosol experiments with Y. pestis; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).[18]

A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.[19]

The plague bacterium could develop drug-resistance and again become a major health threat. One case of a drug-resistant form of the bacterium was found in Madagascar in 1995.[21] Further outbreaks in Madagascar were reported in November 2014[22] and October 2017[23].

Plague has a long history as a biological weapon. Historical accounts from ancient China and medieval Europe detail the use of infected animal carcasses, such as cows or horses, and human carcasses, by the Xiongnu/Huns, Mongols, Turks and other groups, to contaminate enemy water supplies. Han Dynasty General Huo Qubing is recorded to have died of such a contamination while engaging in warfare against the Xiongnu. Plague victims were also reported to have been tossed by catapult into cities under siege.

In 1347, the Genoese possession of Caffa, a great trade emporium on the Crimean peninsula, came under siege by an army of Mongol warriors of the Golden Horde under the command of Janibeg. After a protracted siege during which the Mongol army was reportedly withering from the disease, they decided to use the infected corpses as a biological weapon. The corpses were catapulted over the city walls, infecting the inhabitants. This event might have led to the transfer of the plague (Black Death) via their ships into the south of Europe, possibly explaining its rapid spread.[24]

Ishii innovated bombs containing live mice and fleas, with very small explosive loads, to deliver the weaponized microbes, overcoming the problem of the explosive killing the infected animal and insect by the use of a ceramic, rather than metal, casing for the warhead. While no records survive of the actual usage of the ceramic shells, prototypes exist and are believed to have been used in experiments during WWII.

After World War II, both the United States and the Soviet Union developed means of weaponising pneumonic plague. Experiments included various delivery methods, vacuum drying, sizing the bacterium, developing strains resistant to antibiotics, combining the bacterium with other diseases (such as diphtheria), and genetic engineering. Scientists who worked in USSR bio-weapons programs have stated that the Soviet effort was formidable and that large stocks of weaponised plague bacteria were produced. Information on many of the Soviet projects is largely unavailable. Aerosolized pneumonic plague remains the most significant threat.[citation needed]

The plague can be easily treated with antibiotics, which some countries, such as the United States, have large supplies on hand if such an attack should occur, thus making the threat less severe.[26]

1.
Fluorescent tag
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Generally, fluorescent tagging, or labeling, uses a reactive derivative of a fluorescent molecule known as a fluorophore. The fluorophore selectively binds to a region or functional group on the target molecule. Various labeling techniques such as enzymatic labeling, protein labeling, Ethidium bromide, fluorescein and green fluorescent protein are common tags. The most commonly labelled molecules are antibodies, proteins, amino acids, the development of methods to detect and identify biomolecules has been motivated by the ability to improve the study of molecular structure and interactions. Before the technology of fluorescent labeling, radioisotopes were used to detect, since then, safer methods have been developed that involve the use of fluorescent dyes or fluorescent proteins as tags or probes as a means to label and identify biomolecules. Although fluorescent tagging in this regard has only been recently utilized, sir George Stokes developed the Stokes Law of Fluorescence in 1852 which states that the wavelength of fluorescence emission is greater than that of the exciting radiation. Richard Meyer then termed fluorophore in 1897 to describe a group associated with fluorescence. Since then, Fluorescein was created as a fluorescent dye by Adolph von Baeyer in 1871, within the past century, Ethidium bromide and variants were developed in the 1950s, and in 1994, fluorescent proteins or FPs were introduced. Green fluorescent protein or GFP was discovered by Osamu Shimomura in the 1960s and was developed as a molecule by Douglas Prasher in 1987. FPs led to a breakthrough of live cell imaging with the ability to selectively tag genetic protein regions and observe protein functions, for this breakthrough, Shimomura was awarded the Nobel Prize in 2008. In recent years, new methods for tracking biomolecules have been developed including the use of biosensors, photochromic compounds, biomaterials. Fluorescent labeling is also a method in which applications have expanded to enzymatic labeling, chemical labeling, protein labeling. There are currently several labeling methods for tracking biomolecules, some of the methods include the following. Common species that isotope markers are used for include proteins, in this case, amino acids with stable isotopes of either carbon, nitrogen, or hydrogen are incorporated into polypeptide sequences. These polypeptides are then put through mass spectrometry, because of the exact defined change that these isotopes incur on the peptides, it is possible to tell through the spectrometry graph which peptides contained the isotopes. By doing so, one can extract the protein of interest from others in a group. Isotopic compounds play an important role as photochromes, described below, biosensors are attached to a substance of interest. Normally, this substance would not be able to absorb light, additionally, biosensors that are fluorescent can be viewed with the naked eye

2.
Lymph node
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A lymph node or lymph gland, is an ovoid or kidney-shaped organ of the lymphatic system, and of the adaptive immune system, that is widely present throughout the body. They are linked by the vessels as a part of the circulatory system. Lymph nodes are major sites of B and T lymphocytes, Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells. Lymph nodes do not have a function, which is primarily dealt with by the liver. In the lymphatic system the lymph node is a secondary lymphoid organ, a lymph node is enclosed in a fibrous capsule and is made up of an outer cortex and an inner medulla. Lymph nodes also have clinical significance and they become inflamed or enlarged in various diseases which may range from trivial throat infections, to life-threatening cancers. The condition of the nodes is very important in cancer staging, which decides the treatment to be used. When swollen, inflamed or enlarged, lymph nodes can be hard, Lymph nodes are kidney or oval shaped and range in size from a few millimeters to about 1–2 cm long. Each lymph node is surrounded by a capsule, which extends inside the lymph node to form trabeculae. The substance of the node is divided into the outer cortex. The cortex is continuous around the medulla except where the medulla comes into contact with the hilum. Thin reticular fibers of reticular connective tissue, and elastin form a supporting meshwork called a reticulin inside the node, B cells, are mainly found in the outer where they are clustered together as follicular B cells in lymphoid follicles and the T cells are mainly in the paracortex. The number and composition of follicles can change especially when challenged by an antigen, elsewhere in the node, there are only occasional leucocytes. As part of the network there are follicular dendritic cells in the B cell follicle. The reticular network not only provides the support, but also the surface for adhesion of the dendritic cells. It allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells. All of these sinuses drain the filtered lymphatic fluid into the medullary sinuses and these vessels are smaller and dont allow the passage of the macrophages so that they remain contained to function within the lymph node. In the course of the lymph, lymphocytes may be activated as part of the immune response

3.
Flea
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Fleas are small flightless insects that form the order Siphonaptera. As external parasites of mammals and birds, they live by consuming the blood of their hosts, adults are up to about 3 mm long and usually brown. Bodies flattened sideways enable them to move through their hosts fur or feathers and they lack wings, and have mouthparts adapted for piercing skin and sucking blood and hind legs adapted for jumping. The latter enable them to leap a distance of some 50 times their body length, larvae are worm-like with no limbs, they have chewing mouthparts and feed on organic debris. Over 2,500 species of fleas have been described worldwide, the Siphonaptera are most closely related to the snow scorpionflies, placing them within the endopterygote insect order Mecoptera. Fleas arose in the early Cretaceous, most likely as ectoparasites of mammals and marsupials, each species of flea is more or less a specialist on its host animal species, many species never breed on any other host, though some are less selective. The oriental rat flea, Xenopsylla cheopis, is a vector of Yersinia pestis, the disease was spread by rodents such as the black rat, which were bitten by fleas that then infected humans. Major outbreaks included the Plague of Justinian and the Black Death, both of which killed a sizeable fraction of the worlds population. Fleas appear in human culture in such forms as flea circuses, poems like John Donnes erotic The Flea, works of music such as by Modest Mussorgsky. Flea legs end in strong claws that are designed to grasp a host, unlike other insects, fleas do not possess compound eyes but instead only have simple eyespots with a single biconvex lens, some species lack eyes altogether. Their bodies are compressed, permitting easy movement through the hairs or feathers on the hosts body. The flea body is covered with hard plates called sclerites and these sclerites are covered with many hairs and short spines directed backward, which also assist its movements on the host. The tough body is able to withstand great pressure, likely an adaptation to survive attempts to eliminate them by scratching, fleas lay tiny, white, oval eggs. The larvae are small and pale, have bristles covering their bodies, lack eyes. The larvae feed on organic matter, especially the feces of mature fleas, adults feed only on fresh blood. Immediately before the jump, muscles contract and deform the resilin pad, to prevent premature release of energy or motions of the leg, the flea employs a catch mechanism. Early in the jump, the tendon of the primary jumping muscle passes slightly behind the coxa-trochanter joint, generating a torque which holds the joint closed with the leg close to the body. To trigger jumping, another muscle pulls the tendon forward until it passes the joint axis, generating the opposite torque to extend the leg, the actual take off has been shown by high-speed video to be from the tibiae and tarsi rather than from the trochantera

4.
Democratic Republic of the Congo
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The Democratic Republic of the Congo, also known as DR Congo, DRC, DROC, East Congo, Congo-Kinshasa, or simply the Congo is a country located in Central Africa. From 1971 to 1997 it was named, and is still called, Zaire. It is the second-largest country in Africa by area and eleventh largest in the world, the Congolese Civil Wars, which began in 1996, brought about the end of Mobutu Sese Sekos 32-year reign and devastated the country. These wars ultimately involved nine African nations, multiple groups of UN peacekeepers and twenty armed groups, besides the capital, Kinshasa, the other major cities, Lubumbashi and Mbuji-Mayi, are both mining communities. DR Congos largest export is raw minerals, with China accepting over 50% of DRCs exports in 2012, as of 2015, according to the Human Development Index, DR Congo has a low level of human development, ranking 176 out of 187 countries. The country was known officially as the Democratic Republic of the Congo from 1965 to 27 October 1971, in 1992, the Sovereign National Conference voted to change the name of the country to the Democratic Republic of the Congo, but the change was not put into practice. The countrys name was restored by former president Laurent-Désiré Kabila following the fall of longtime dictator Mobutu Sese Seko in 1997, some historians think that Bantu peoples began settling in the extreme northwest of Central Africa at the beginning of the 5th century and then gradually started to expand southward. Their propagation was accelerated by the transition from Stone Age to Iron Age techniques, the people living in the south and southwest were mostly San Bushmen and hunter-gatherer groups, whose technology involved only minimal use of metal technologies. The development of tools during this time period revolutionized agriculture. This led to the displacement of the groups in the east and southeast. The 10th century marked the expansion of the Bantu in West-Central Africa. Rising populations soon made intricate local, regional and foreign commercial networks that traded mostly in salt, iron. Belgian exploration and administration took place from the 1870s until the 1920s and it was first led by Sir Henry Morton Stanley, who undertook his explorations under the sponsorship of King Leopold II of Belgium. The eastern regions of the precolonial Congo were heavily disrupted by constant slave raiding, mainly from Arab–Swahili slave traders such as the infamous Tippu Tip, Leopold had designs on what was to become the Congo as a colony. Leopold formally acquired rights to the Congo territory at the Conference of Berlin in 1885 and he named it the Congo Free State. Leopolds rėgime began various infrastructure projects, such as construction of the railway ran from the coast to the capital of Leopoldville. Nearly all such projects were aimed at making it easier to increase the assets which Leopold. In the Free State, colonists brutalized the local population into producing rubber, for which the spread of automobiles, rubber sales made a fortune for Leopold, who built several buildings in Brussels and Ostend to honor himself and his country

5.
Madagascar
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Madagascar, officially the Republic of Madagascar, and previously known as the Malagasy Republic, is an island country in the Indian Ocean, off the coast of Southeast Africa. The nation comprises the island of Madagascar, and numerous smaller peripheral islands, consequently, Madagascar is a biodiversity hotspot, over 90% of its wildlife is found nowhere else on Earth. The islands diverse ecosystems and unique wildlife are threatened by the encroachment of the growing human population. The first archaeological evidence for human foraging on Madagascar dates to 2000 BC, human settlement of Madagascar occurred between 350 BC and AD550 by Austronesian peoples arriving on outrigger canoes from Borneo. These were joined around AD1000 by Bantu migrants crossing the Mozambique Channel from East Africa, other groups continued to settle on Madagascar over time, each one making lasting contributions to Malagasy cultural life. The Malagasy ethnic group is divided into 18 or more sub-groups of which the largest are the Merina of the central highlands. Until the late 18th century, the island of Madagascar was ruled by an assortment of shifting sociopolitical alliances. Beginning in the early 19th century, most of the island was united and ruled as the Kingdom of Madagascar by a series of Merina nobles, the monarchy collapsed in 1897 when the island was absorbed into the French colonial empire, from which the island gained independence in 1960. The autonomous state of Madagascar has since undergone four major constitutional periods, since 1992, the nation has officially been governed as a constitutional democracy from its capital at Antananarivo. However, in an uprising in 2009, president Marc Ravalomanana was made to resign. Constitutional governance was restored in January 2014, when Hery Rajaonarimampianina was named president following a 2013 election deemed fair, Madagascar is a member of the United Nations, the Organisation Internationale de la Francophonie and the Southern African Development Community. Madagascar belongs to the group of least developed countries, according to the United Nations, Malagasy and French are both official languages of the state. The majority of the population adheres to traditional beliefs, Christianity, ecotourism and agriculture, paired with greater investments in education, health, and private enterprise, are key elements of Madagascars development strategy. As of 2017, the economy has been weakened by the 2009-2013 political crisis, in the Malagasy language, the island of Madagascar is called Madagasikara and its people are referred to as Malagasy. The islands appellation Madagascar is not of origin, but rather was popularized in the Middle Ages by Europeans. On St. Laurences Day in 1500, Portuguese explorer Diogo Dias landed on the island, polos name was preferred and popularized on Renaissance maps. At 592,800 square kilometres, Madagascar is the worlds 47th largest country, the country lies mostly between latitudes 12°S and 26°S, and longitudes 43°E and 51°E. Neighboring islands include the French territory of Réunion and the country of Mauritius to the east, as well as the state of Comoros, the nearest mainland state is Mozambique, located to the west

6.
Peru
–
Peru, officially the Republic of Peru, is a country in western South America. It is bordered in the north by Ecuador and Colombia, in the east by Brazil, in the southeast by Bolivia, in the south by Chile, and in the west by the Pacific Ocean. Peruvian territory was home to ancient cultures spanning from the Norte Chico civilization in Caral, one of the oldest in the world, to the Inca Empire, the largest state in Pre-Columbian America. The Spanish Empire conquered the region in the 16th century and established a Viceroyalty with its capital in Lima, ideas of political autonomy later spread throughout Spanish America and Peru gained its independence, which was formally proclaimed in 1821. After the battle of Ayacucho, three years after proclamation, Peru ensured its independence, subsequently, the country has undergone changes in government from oligarchic to democratic systems. Peru has gone through periods of political unrest and internal conflict as well as periods of stability, Peru is a representative democratic republic divided into 25 regions. It is a country with a high Human Development Index score. Its main economic activities include mining, manufacturing, agriculture and fishing, the Peruvian population, estimated at 31.2 million in 2015, is multiethnic, including Amerindians, Europeans, Africans and Asians. The main spoken language is Spanish, although a significant number of Peruvians speak Quechua or other native languages and this mixture of cultural traditions has resulted in a wide diversity of expressions in fields such as art, cuisine, literature, and music. The name of the country may be derived from Birú, the name of a ruler who lived near the Bay of San Miguel, Panama. When his possessions were visited by Spanish explorers in 1522, they were the southernmost part of the New World yet known to Europeans, thus, when Francisco Pizarro explored the regions farther south, they came to be designated Birú or Perú. An alternative history is provided by the contemporary writer Inca Garcilasco de la Vega, son of an Inca princess, the Spanish Crown gave the name legal status with the 1529 Capitulación de Toledo, which designated the newly encountered Inca Empire as the province of Peru. Under Spanish rule, the country adopted the denomination Viceroyalty of Peru, the earliest evidences of human presence in Peruvian territory have been dated to approximately 9,000 BC. Andean societies were based on agriculture, using such as irrigation and terracing, camelid husbandry. Organization relied on reciprocity and redistribution because these societies had no notion of market or money, the oldest known complex society in Peru, the Norte Chico civilization, flourished along the coast of the Pacific Ocean between 3,000 and 1,800 BC. These early developments were followed by archaeological cultures that developed mostly around the coastal, the Cupisnique culture which flourished from around 1000 to 200 BC along what is now Perus Pacific Coast was an example of early pre-Incan culture. The Chavín culture that developed from 1500 to 300 BC was probably more of a religious than a political phenomenon, on the coast, these included the civilizations of the Paracas, Nazca, Wari, and the more outstanding Chimu and Mochica. Their capital was at Chan Chan outside of modern-day Trujillo, in the 15th century, the Incas emerged as a powerful state which, in the span of a century, formed the largest empire in pre-Columbian America with their capital in Cusco

7.
Rodent
–
Rodents are mammals of the order Rodentia, which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all species are rodents, they are found in vast numbers on all continents except Antarctica. They are the most diversified mammalian order and live in a variety of terrestrial habitats, Species can be arboreal, fossorial, or semiaquatic. Well-known rodents include mice, rats, squirrels, prairie dogs, porcupines, beavers, guinea pigs, hamsters, and capybaras. Other animals such as rabbits, hares, and pikas, whose incisors also grow continually, were included with them, but are now considered to be in a separate order. Nonetheless, Rodentia and Lagomorpha are sister groups, sharing a most recent common ancestor, most rodents are small animals with robust bodies, short limbs, and long tails. They use their incisors to gnaw food, excavate burrows. Most eat seeds or other plant material, but some have more varied diets and they tend to be social animals and many species live in societies with complex ways of communicating with each other. Mating among rodents can vary from monogamy, to polygyny, to promiscuity, many have litters of underdeveloped, altricial young, while others are precocial at birth. The rodent fossil record back to the Paleocene on the supercontinent of Laurasia. Rodents greatly diversified in the Eocene, as spread across continents. Rodents reached both South America and Madagascar from Africa, and were the only placental mammals to reach. Rodents have been used as food, for clothing, as pets, some species, in particular the brown rat, the black rat, and the house mouse, are serious pests, eating and spoiling food stored by humans, and spreading diseases. The distinguishing feature of the rodents is their pairs of continuously growing and these incisors have thick layers of enamel on the front and little enamel on the back. Because they do not stop growing, the animal must continue to wear them down so that they do not reach and pierce the skull. As the incisors grind against each other, the softer dentine on the rear of the teeth wears away, most species have up to 22 teeth with no canines or anterior premolars. A gap, or diastema, occurs between the incisors and the teeth in most species. This allows rodents to suck in their cheeks or lips to shield their mouth and throat from wood shavings and other inedible material, chinchillas and guinea pigs have a high-fiber diet, their molars have no roots and grow continuously like their incisors

8.
Interstitial fluid
–
Interstitial fluid or tissue fluid is a solution that bathes and surrounds the tissue cells of multicellular animals. It is the component of the extracellular fluid, which also includes plasma. The interstitial fluid is found in the interstices - the spaces between cells, on average, a person has about 10 litres of interstitial fluid, providing the cells of the body with nutrients and a means of waste removal. Plasma and interstitial fluid are very similar and this similarity exists because water, ions, and small solutes are continuously exchanged between plasma and interstitial fluids across the walls of capillaries. Plasma, the component in blood, communicates freely with interstitial fluid through pores. Hydrostatic pressure is generated by the force of the heart. It pushes water out of the capillaries, the water potential is created due to the inability of certain blood proteins to pass through the walls of capillaries. The build-up of these proteins within the capillaries induces osmosis, the water passes from a high concentration outside of the vessels to a low concentration inside of the vessels, in an attempt to reach an equilibrium. The osmotic pressure drives water back into the vessels, because the blood in the capillaries is constantly flowing, equilibrium is never reached. The balance between the two forces differs at different points on the capillaries, at the arterial end of a vessel, the hydrostatic pressure is greater than the osmotic pressure, so the net movement favors water and other solutes being passed into the tissue fluid. At the venous end, the pressure is greater, so the net movement favors substances being passed back into the capillary. This difference is created by the direction of the flow of blood, to prevent a build-up of tissue fluid surrounding the cells in the tissue, complementing the venous system is the lymphatic system, which plays a part in the transport of tissue fluid. Tissue fluid can pass into the lymph vessels, and eventually ends up rejoining the blood. Sometimes the removal of fluid does not function correctly. This can cause swelling, often around the feet and ankles, the position of swelling is due to the effects of gravity. Interstitial fluid consists of a solvent containing sugars, salts, fatty acids, amino acids, coenzymes, hormones, neurotransmitters, white blood cells. This water solvent accounts for 26% of the water in the human body, the composition of tissue fluid depends upon the exchanges between the cells in the biological tissue and the blood. This means that tissue fluid has a different composition in different tissues, not all of the contents of the blood pass into the tissue, which means that tissue fluid and blood are not the same

9.
Bacteria
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Bacteria constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods, Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology, There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are approximately 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants, Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of bodies and bacteria are responsible for the putrefaction stage in this process. In March 2013, data reported by researchers in October 2012, was published and it was suggested that bacteria thrive in the Mariana Trench, which with a depth of up to 11 kilometres is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, You can find microbes everywhere—theyre extremely adaptable to conditions, the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial particularly in the gut flora. However several species of bacteria are pathogenic and cause diseases, including cholera, syphilis, anthrax, leprosy. The most common fatal diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year. In developed countries, antibiotics are used to treat infections and are also used in farming, making antibiotic resistance a growing problem. Once regarded as constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and these evolutionary domains are called Bacteria and Archaea. The ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, for about 3 billion years, most organisms were microscopic, and bacteria and archaea were the dominant forms of life. In 2008, fossils of macroorganisms were discovered and named as the Francevillian biota, however, gene sequences can be used to reconstruct the bacterial phylogeny, and these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. Bacteria were also involved in the second great evolutionary divergence, that of the archaea, here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves possibly related to the Archaea

10.
Lymphatic system
–
The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the cardiovascular system, the system is not a closed system. The human circulatory system processes an average of 20 liters of blood per day through capillary filtration, roughly 17 litres of the filtered plasma are reabsorbed directly into the blood vessels, while the remaining three litres remain in the interstitial fluid. One of the functions of the lymph system is to provide an accessory return route to the blood for the surplus three litres. The other main function is that of defense in the immune system, lymph is very similar to blood plasma, it contains lymphocytes and other white blood cells. It also contains waste products and cellular debris together with bacteria, associated organs composed of lymphoid tissue are the sites of lymphocyte production. Lymphocytes are concentrated in the lymph nodes, the spleen and the thymus are also lymphoid organs of the immune system. The tonsils are lymphoid organs that are associated with the digestive system. Lymphoid tissues contain lymphocytes, and also other types of cells for support. Lymph is the fluid that is formed when interstitial fluid enters the lymphatic vessels of the lymphatic system. Eventually, the lymph vessels empty into the ducts, which drain into one of the two subclavian veins, near their junction with the internal jugular veins. The lymphatic system consists of lymphatic organs, a network of lymphatic vessels. The primary or central lymphoid organs generate lymphocytes from immature progenitor cells, the thymus and the bone marrow constitute the primary lymphoid organs involved in the production and early clonal selection of lymphocyte tissues. Bone marrow is responsible for both the creation of T cells and the production and maturation of B cells, from the bone marrow, B cells immediately join the circulatory system and travel to secondary lymphoid organs in search of pathogens. T cells, on the hand, travel from the bone marrow to the thymus. Mature T cells join B cells in search of pathogens, the other 95% of T cells begin a process of apoptosis, a form of programmed cell death. Secondary or peripheral lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes, the peripheral lymphoid organs are the sites of lymphocyte activation by antigens. Activation leads to clonal expansion and affinity maturation, mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific antigen

11.
Phagocytosis
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In cell biology, phagocytosis is the process by which a cell—often a phagocyte or a protist—engulfs a solid particle to form an internal compartment known as a phagosome. It is distinct from other forms of endocytosis like pinocytosis that involves the internalization of extracellular liquids, phagocytosis is involved in the acquisition of nutrients for some cells. In an organisms immune system, phagocytosis is a mechanism used to remove pathogens. For example, when a macrophage ingests a pathogenic microorganism, the pathogen becomes trapped in a phagosome which then fuses with a lysosome to form a phagolysosome, within the phagolysosome, enzymes and toxic peroxides digest the pathogen. Bacteria, dead cells, and small mineral particles are all examples of objects that may be phagocytized. The process has triggered the name Phagocytes for the 1st line of defence in the immune system, phagocytosis was first noted by Canadian physician William Osler, and later studied and named by Élie Metchnikoff. Phagocytosis in mammalian cells is activated by attachment to pathogen-associated molecular patterns. Opsonins such as C3b and antibodies can act as attachment sites, engulfment of material is facilitated by the actin-myosin contractile system. The phagosome of ingested material is fused with the lysosome, forming a phagolysosome. Degradation can be oxygen-dependent or oxygen-independent, oxygen-dependent degradation depends on NADPH and the production of reactive oxygen species. Hydrogen peroxide and myeloperoxidase activate a system, which leads to the creation of hypochlorite. Oxygen-independent degradation depends on the release of granules, containing proteolytic enzymes such as defensins, lysozyme, other antimicrobial peptides are present in these granules, including lactoferrin, which sequesters iron to provide unfavourable growth conditions for bacteria. It is possible for other than dedicated phagocytes to engage in phagocytosis. Some white blood cells in human immune system perform phagocytosis by gulping in some pathogenic, following apoptosis, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called efferocytosis. Defects in apoptotic cell clearance is usually associated with impaired phagocytosis of macrophages, in many protists, phagocytosis is used as a means of feeding, providing part or all of their nourishment. This is called phagotrophic nutrition, distinguished from osmotrophic nutrition which takes place by absorption, in some, such as amoeba, phagocytosis takes place by surrounding the target object with pseudopods, as in animal phagocytes. In humans, entamoeba histolytica can phagocytose red blood cells, Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide

12.
Yersinia pestis
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Yersinia pestis is a Gram-negative, rod-shaped coccobacillus, a facultative anaerobic organism that can infect humans via the oriental rat flea. It causes the disease called bubonic plague. Human Y. pestis infection takes three forms, pneumonic, septicemic, and bubonic plagues. These plagues probably originated in China and were transmitted west via trade routes, Y. pestis was discovered in 1894 by Alexandre Yersin, a Swiss/French physician and bacteriologist from the Pasteur Institute, during an epidemic of the plague in Hong Kong. Yersin was a member of the Pasteur school of thought, kitasato Shibasaburō, a German-trained Japanese bacteriologist who practised Kochs methodology, was also engaged at the time in finding the causative agent of the plague. However, Yersin actually linked plague with Y. pestis, named Pasteurella pestis in the past, the organism was renamed Yersinia pestis in 1944. Every year, thousands of cases of the plague are still reported to the World Health Organization, although, with proper treatment, the prognosis for victims is now much better. A five- to six-fold increase in cases occurred in Asia during the time of the Vietnam War, possibly due to the disruption of ecosystems, the plague also has a detrimental effect on non-human mammals. In the United States, mammals such as the prairie dog. Y. pestis is a non-motile, stick-shaped, facultative anaerobic bacterium with bipolar staining that produces an anti-phagocytic slime layer, similar to other Yersinia species, it tests negative for urease, lactose fermentation, and indole. The closest relative is the gastrointestinal pathogen Yersinia pseudotuberculosis, and more distantly Yersinia enterocolitica, the complete genomic sequence is available for two of the three subspecies of Y. pestis, strain KIM, and strain CO92. As of 2006, the sequence of a strain of biovar Antiqua has been recently completed. Similar to the pathogenic strains, there are signs of loss of function mutations. The chromosome of strain KIM is 4,600,755 base pairs long, like Y. pseudotuberculosis and Y. enterocolitica, Y. pestis is host to the plasmid pCD1. In addition, it hosts two other plasmids, pPCP1 and pMT1 that are not carried by the other Yersinia species. PFra codes for a phospholipase D that is important for the ability of Y. pestis to be transmitted by fleas, pPla codes for a protease, Pla, that activates plasmin in human hosts and is a very important virulence factor for pneumonic plague. Together, these plasmids, and a pathogenicity island called HPI, encode proteins that cause the pathogenesis. Y. pestis is thought to be descendant from Y. pseudotuberculosis, a comprehensive and comparative proteomics analysis of Y. pestis strain KIM was performed in 2006

Oriental rat flea (Xenopsylla cheopis) infected with the Y. pestis bacterium which appears as a dark mass in the gut: The foregut (proventriculus) of this flea is blocked by a Y. pestis biofilm; when the flea attempts to feed on an uninfected host, Y. pestis is regurgitated into the wound, causing infection.